DESCRIPTION: (Principal Investigator's) This research proposal reflects our general interest in the development of new reagents in the context of acyclic stereocontrol. Once the reaction methodology has achieved success in the development stage, it is used in the asymmetric synthesis of complex organic molecules that may have relevance in the treatment of human diseases. The long term objectives are the eventual achievement of the asymmetric synthesis of th macrolide antibiotics, rutamycin B, oligomycin C, oleanolide, discodermolide, and the proteosome inhibitor lactacystin. In this regard, we intend to 1. explore the scope of double stereodifferentiating reactions of chiral allylsilane reagents with chiral aldehyde partners. This study will be used to determine their potential utility for polypropionate assemblage as well as vicinal amino alcohols. As a new direction for this technology we will develop novel approaches to the synthesis of new allylsilane reagents bearing C-centered chirality; allylsilanes and beta-substituted (E)-crotylsilanes. These approaches include the development of chiral Lewis acids to promote asymmetric (2,3) and (3,3)-sigmatropic processes. 2. Pursue the completion of the synthesis of polypropionate derived macrolide antibiotics, rutamycin B and oligomycin C. 3. Pursue the total synthesis of the macrolide antibiotic oleanolide. 4. Pursue the total synthesis of the microtubule stabilizing agent discodermolide. 5. Pursue the total synthesis of unusual amino acid (+)-lactacystin.